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Inhaling antibiotics to treat temporary worsening of lung infection in people with cystic fibrosis

Review question

We reviewed the evidence for inhaling antibiotics to treat exacerbations (flare ups) of lung infection in people with cystic fibrosis.

Background

Cystic fibrosis is a serious genetic disorder that results in abnormally sticky mucus in several parts of the body. In the lungs the sticky mucus can lead to repeated infection. An exacerbation makes the symptoms more severe. Antibiotics are an essential part of treatment and may be given by mouth, by needle into the blood stream or by inhaling the drug. We wanted to learn if inhaling antibiotics improved general health compared to the other methods.

This might mean that people with cystic fibrosis could avoid hospitalisation for intravenous antibiotics and some side effects. Inhaling the antibiotics would also be easier for people who have difficulty with access to their veins. This is an updated version of the review.

Search date

The evidence is current to: 09 October 2018.

Study characteristics

We found four trials with a total of 167 participants, two of which compared inhaled antibiotics alone to intravenous antibiotics alone (77 participants) and two which compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone (90 participants) for treating exacerbations in people with cystic fibrosis. In all trials the inhaled antibiotics were compared to the same antibiotics given intravenously. The numbers of participants in each trial ranged from 18 to 62.

Key results

Inhaled antibiotics alone versus intravenous antibiotics alone

One trial (18 participants) reported a perceived improvement in lifestyle in both groups but neither trial reported on time off work or school. Both trials measured lung function, but neither reported any difference between treatment groups. One trial (18 participants) reported no difference in the need for additional antibiotics and the second trial (59 participants) reported on the time to next exacerbation - there was no difference between inhaled or intravenous antibiotics for either outcome. Only one trial (18 participants) measured adverse events and sputum microbiology, but did not find any difference between treatments for either outcome.

Neither trial reported on quality of life or time off work or school. Both trials reported lung function, but found no difference between groups. Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (28 participants) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events and one trial (62 participants) reported no difference in the emergence of antibiotic-resistant organisms.

Quality of the evidence

We graded the quality of the evidence as very low. We had concerns since none of the trials stated how the participants were diagnosed with CF or how they defined an exacerbation. It was not possible to keep the treatment group secret from the participants as the trials compared different ways of giving the antibiotics and we thought this would likely influence some of the results. We were not sure whether the participants were put into the different groups truly at random and we do not know how this might affect the results.

Authors' conclusions:

There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

Read the full abstract...

Background:

Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review.

Objectives:

To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival.

Search strategy:

We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 03 October 2018.

We searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 09 October 2018.

Selection criteria:

Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks.

Data collection and analysis:

Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the quality of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information.

Main results:

Four trials with 167 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and two trials (90 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials, but for all trials we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis.

Inhaled antibiotics alone versus intravenous antibiotics alone

Only one trial (n = 18) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-quality of evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-quality evidence). With regards to our secondary outcomes, one trial (n = 18) reported no difference in the need for additional antibiotics and the second trial (n = 59) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-quality evidence). The single trial (n = 18) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-quality evidence).

Neither trial reported on quality of life or time off work or school. Both trials measured lung function, but found no difference between groups in forced expiratory volume in one second (one trial, n = 28, very low-quality evidence) or vital capacity (one trial, n = 62). Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (n = 28) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events (very low-quality evidence) and one trial (n = 62) reported no difference in the emergence of antibiotic-resistant organisms (very low-quality evidence).